title: Brain regional α-[11C]methyl-L-tryptophan trapping in medication-free patients with obsessive-compulsive disorder.
abstract: BACKGROUND
  The hypothesis of a serotonin (5-hydroxytryptamine [5-HT]) dysfunction in obsessive-compulsive disorder (OCD) stems largely from the clinical efficacy of 5-HT reuptake inhibitors. Serotonergic abnormalities in the unmedicated symptomatic state, however, remain to be fully characterized.
  
  
  OBJECTIVE
  To investigate brain regional 5-HT synthesis, as indexed by positron emission tomography and the α-[(11)C]methyl-L-tryptophan trapping constant (K*), in treatment-free adults meeting criteria for OCD.
  
  
  METHODS
  Between-group comparison.
  
  
  METHODS
  Department of Psychiatry and Montreal Neurological Institute, McGill University, and Department of Psychology, McGill University Health Centre, Quebec, Canada.
  
  
  METHODS
  Twenty-one medication-free patients with OCD (15 men with a mean [SD] age of 33.2 [9.3] years and 6 women with a mean [SD] age of 35.8 [7.1] years) and 21 healthy controls matched for age and sex (15 men with a mean [SD] age of 32.9 [10.1] years and 6 women with a mean [SD] age of 36.5.5 [8.6] years). Main Outcome Measure The α-[(11)C]methyl-L-tryptophan brain trapping constant K*, which was analyzed with Statistical Parametric Mapping (SPM8) and with proportional normalization (extent threshold of 100 voxels with a peak threshold of P ≤ .005).
  
  
  RESULTS
  Compared with healthy controls, the patients with OCD exhibited significantly greater α-[(11)C]methyl-L-tryptophan trapping in the right hippocampus and left temporal gyrus (Brodmann area 20). In the larger subsample of all men, these same differences were also evident, as well as higher K* values in the caudate nucleus. Individual differences in symptom severity correlated positively with K* values sampled from the caudate and temporal lobe of the patients with OCD, respectively. There were no regions where the patients exhibited abnormally low K* values. Volumetric analyses found no morphometric alterations that would account for the group differences.
  
  
  CONCLUSIONS
  The results support previous reports of greater striatal and temporal lobe activity in patients with OCD than in healthy controls and suggest that these disturbances include a serotonergic component. Previously reported glucose metabolic disturbances in OCD involving the orbitofrontal and cingulate cortices, in comparison, might reflect postsynaptic changes in the serotonergic system.
authors.affiliation: DERBH, Department of Psychiatry, McGill University, 1033 Pine Ave West, Montreal, QC H3A 1A1, Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Berney
authors.forename: Marco
authors.initials: M
authors.lastname: Leyton
authors.forename: Paul
authors.initials: P
authors.lastname: Gravel
authors.forename: Igor
authors.initials: I
authors.lastname: Sibon
authors.forename: Debbie
authors.initials: D
authors.lastname: Sookman
authors.forename: Pedro
authors.initials: P
authors.lastname: Rosa Neto
authors.forename: Mirko
authors.initials: M
authors.lastname: Diksic
authors.forename: Akio
authors.initials: A
authors.lastname: Nakai
authors.forename: Gilbert
authors.initials: G
authors.lastname: Pinard
authors.forename: Christo
authors.initials: C
authors.lastname: Todorov
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Okazawa
authors.forename: Pierre
authors.initials: P
authors.lastname: Blier
authors.forename: Thomas Edward
authors.initials: TE
authors.lastname: Nordahl
authors.forename: Chawki
authors.initials: C
authors.lastname: Benkelfat
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000378:metabolism*; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000378:metabolism*; D049268:Positron-Emission Tomography; D013702:Temporal Lobe / Q000378:metabolism; D014364:Tryptophan / Q000031:analogs & derivatives* / Q000378:metabolism; D055815:Young Adult
chemical_list: C020774:alpha-methyltryptophan; D014364:Tryptophan